Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional gastrointestinal diseases (FGIDs) are often noticed disturbances. Functional dyspepsia (FD) is the most frequent FGID of the upper part of the gastrointestinal tract while irritable bowel syndrome (IBS) occurs in the lower gastrointestinal part. Both clinical entities are characterized by rich symptomatology and the pattern of the diagnostic guidelines. Recognition and the classification of FGIDs are difficult, consisting in exclusion of all possible organic disorders and subordinating on the predominant symptom basis to most appropriate class, acording to Rome III classification. The present FGIDs pharmacotherapy is limited mostly to the symptomatical treatment and it is based on medicines conventionally used in various gastrointestinal organic illnesses (antisecretory, gastroprotective agents, antidiarrhoeal and laxative drugs). Some of them which seem to diminish visceral hypersensitivity acting via serotonin receptors are also used, including 5-HT4 agonists and 5-HT3 antagonists. Many investigations over the new causal acting medicines last at present, which would be able to abolish the main pathophysiological FD and IBS mechanisms: visceral hypersensitivity and both myoelectrical and dysmotility phenomena. Thus, new pharmacological agents influencing opioid, purinergic, NMDA, CCK-A, or NK receptors are studied. The article is the mini-review, representing classification and the outline of the FGIDs pathogenesis, the present concepts of their pharmacological treatment and the future perspectives of pharmacoherapy with the use of new, interfering into key pathomechanisms drugs.
 ...
PMID:Pathophysiological concepts of functional dyspepsia and irritable bowel syndrome future pharmacotherapy. 1989 40

Chronic stress produces maladaptive pain responses, manifested as alterations in pain processing and exacerbation of chronic pain conditions including irritable bowel syndrome. Female predominance, especially during reproductive years, strongly suggests a role of gonadal hormones. However, gonadal hormone modulation of stress-induced pain hypersensitivity is not well understood. In the present study, we tested the hypothesis that estradiol is pronociceptive and testosterone is antinociceptive in a model of stress-induced visceral hypersensitivity (SIVH) in rats by recording the visceromotor response to colorectal distention after a 3-day forced swim (FS) stress paradigm. FS induced visceral hypersensitivity that persisted at least 2 weeks in female, but only 2 days in male rats. Ovariectomy blocked and orchiectomy facilitated SIVH. Furthermore, estradiol injection in intact male rats increased SIVH and testosterone in intact female rats attenuated SIVH. Western blot analyses indicated estradiol increased excitatory glutamate ionotropic receptor NMDA type subunit 1 expression and decreased inhibitory metabotropic glutamate receptor 2 expression after FS in male thoracolumbar spinal cord. In addition, the presence of estradiol during stress increased spinal brain-derived neurotrophic factor (BDNF) expression independent of sex. In contrast, testosterone blocked the stress-induced increase in BDNF expression in female rats. These data suggest that estradiol facilitates and testosterone attenuates SIVH by modulating spinal excitatory and inhibitory glutamatergic receptor expression.
 ...
PMID:Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats. 2949 40

Cortical areas including the anterior cingulate cortex (ACC) play critical roles in different types of chronic pain. Most of previous studies focus on the sensory inputs from somatic areas, and less information about plastic changes in the cortex for visceral pain. In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch-clamp recording, behavioral tests, western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out mice. Integrative approaches were used to investigate possible changes of neuronal AC1 in the ACC after the injury. We found that AC1, a key enzyme for pain-related cortical plasticity, was significantly increased in the ACC in an animal model of irritable bowel syndrome. Inhibiting AC1 activity by a selective AC1 inhibitor NB001 significantly reduced the up-regulation of AC1 protein in the ACC. Furthermore, we found that AC1 is required for NMDA GluN2B receptor up-regulation and increases of NMDA receptor-mediated currents. These results suggest that AC1 may form a positive regulation in the cortex during chronic visceral pain. Our findings demonstrate that the up-regulation of AC1 protein in the cortex may underlie the pathology of chronic visceral pain; and inhibiting AC1 activity may be beneficial for the treatment of visceral pain.
 ...
PMID:Cyclic AMP-dependent positive feedback signaling pathways in the cortex contributes to visceral pain. 3166 10